Synthesis of an ABCD-Type Phthalocyanine by Intramolecular Cyclization Reaction

Article abstract of DOI:10.1021/acs.orglett.6b01489

Unsymmetrical phthalocyanines with a low symmetry can exhibit unique and intriguing properties that can facilitate their applications in certain disciplines. The synthesis of these compounds, however, has posed a great difficulty. A novel and unprecedente

Full text of DOI:10.1021/acs.orglett.6b01489

Letter
pubs.acs.org/OrgLett
Synthesis of an ABCD-Type Phthalocyanine by Intramolecular
Cyclization Reaction
Sun Y. S. Chow and Dennis K. P. Ng*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
S
* Supporting Information
ABSTRACT: Unsymmetrical phthalocyanines with a low
symmetry can exhibit unique and intriguing properties that can
facilitate their applications in certain disciplines. The synthesis of
these compounds, however, has posed a great difficulty. A novel
and unprecedented approach for phthalocyanine synthesis is
reported that involves intramolecular cyclization of prelinked
tetrakisphthalonitriles. By using this strategy, the first ABCD-type
phthalocyanine has been prepared in 7.2% yield.
eing a versatile class of functional dyes, phthalocyanines
possess intriguing and tunable optoelectronic, photo-
nately, all these methods still suffer from various deficiencies
B
and limitations, which preclude them to be employed generally.
Phthalocyanines with more than two different isoindole units
remain extremely rare.15 We report herein a programmed
synthetic strategy for low-symmetry phthalocyanines, which
involves a preselection and conjugation of four phthalonitrile
precursors followed by a base-promoted intramolecular
cyclization in the presence of a metal template. This controlled
pathway allows tailor-made phthalocyanines to be synthesized
and the preparation of low-symmetry analogues that cannot be
synthesized readily by conventional methods, including the
ABCD-type phthalocyanines. A similar approach has been
reported for the preparation of porphyrins that contain four
different meso-substituents.16 As shown in Scheme 1, 1-
protected 19-acylbilanes undergo intramolecular condensation
under a metal-templating and basic condition to give the
corresponding ABCD-type porphyrins.
physical, catalytic, and self-assembly properties.1 These
characteristics, together with their high stability, render them
useful as advanced materials,2 selective sensors,3 efficient
catalysts,4 and promising theranostic agents5 for various
practical/potential applications. The properties of these macro-
cyclic compounds depend largely on the metal center and the
axial and/or peripheral substituents. Both the nature and
position of the substituents are important, which, apart from
imparting their intrinsic characteristics to the parent macro-
cycles, can control the molecular architecture, which in turn can
alter their physical properties. Therefore, there has been
considerable interest in controlled synthesis of phthalocyanines,
particularly the low-symmetry analogues, which could exhibit
unique properties that cannot be found in the symmetrical
counterparts,6 as well as revealing their structure−property−
activity relationships.
Phthalocyanines are usually prepared by cyclotetramerization
of phthalonitriles or their derivatives, such as 1,3-diiminoisoin-
dolines, phthalimides, and phthalic anhydrides.7 While these
methodologies can effectively produce a wide range of
symmetrical phthalocyanines with four identical aza-linked
isoindole units, the preparation of the unsymmetrical analogues
by mixed condensation of two of these precursors inevitably
gives a mixture of products that may not be separated readily. A
careful selection of precursors and optimization of their ratio
and experimental conditions are crucial to facilitate the isolation
and purification of the A3B-type products.8 Mixed condensation
with more than two of these precursors is not feasible to
prepare phthalocyanines with an even lower symmetry. To
circumvent this problem, a number of alternative synthetic
pathways have been developed for low-symmetry phthalocya-
nines, such as ring expansion of subphthalocyanines,9 polymer-
supported synthesis,10 cross condensation of 1,3,3-trichloro-6/
7-nitroisoindolenine and 1,3-diiminoisoindolines,11 use of
sterically demanding precursors,12 the “half-phthalocyanine”
approach,13 and cyclization of bisphthalonitriles.14 Unfortu-
Scheme 1. Preparation of ABCD-Type Porphyrins
To assess the feasibility of this approach, we first prepared
the tetrakisphthalonitrile 1 through a series of nucleophilic
substitution reactions as shown in Scheme S1 in the Supporting
Information (SI). The four phthalonitrile units were connected
by three 1,3-dioxypropylene linkers, and two tetraethylene
glycol chains were introduced to the ends to increase the
solubility of the resulting phthalocyanine that can facilitate the
Received: May 23, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01489
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
purification. By using conventional base-promoted cyclization
conditions in the presence of Zn(OAc)2 in 1-pentanol, the
desired product 2 could be isolated. Attempts were made to
optimize the yield by changing the reaction conditions,
including the concentration of 1 (0.1−2.0 mg mL−1), nature
of the base [1,8-diazabicylo[5.4.0]undec-7-ene (DBU) or
lithium], ratio of DBU to solvent (1:200 or 1:300), reaction
temperature (140 or 150 °C), and reaction time (up to 48 h).
While the use of lithium and a highly diluted solution (at 0.1
mg mL−1) could not yield the expected product, the yields of 2
were in the range of 2.6−7.3% in the other conditions. The
optimized conditions as given in Scheme 2 and the
Scheme 3. Preparation of ABCD-Type Phthalocyanine 12
Scheme 2. Preparation of Phthalocyanine 2 by
Intramolecular Cyclization of Tetrakisphthalonitrile 1
ABCD-type phthalocyanine 12 was isolated as an isomerically
pure product in 7.2% yield. Again, this compound could be
purified readily by silica gel column chromatography. To our
knowledge, ABCD-type phthalocyanines have never been
reported so far.
Experimental Section in SI could afford 2 in a quite satisfactory
yield (7.3%). As these conditions are typical for preparation of
other metallophthalocyanines,7 the effect of metal salts was not
examined.
All the new compounds were unambiguously characterized
with various spectroscopic methods (see the Experimental
Section in SI). For phthalocyanines 2 and 12, the electrospray
ionization (ESI) mass spectra showed an intense cluster due to
the molecular ion with correct exact mass and isotopic pattern
It was found that a relatively low concentration of
tetrakisphthalonitrile 1 (at 0.4 mg mL−1) was still needed to
promote intramolecular cyclization. In fact, apart from the
phthalocyanine product, which has a characteristic green color,
some very polar, dark brown compounds were also formed and
trapped in the silica gel column. They are supposed to be the
undesired polymeric isoindoles formed by intermolecular
condensation reaction. As compound 2 was the major, if not
the only, phthalocyanine product, its isolation and purification
could be performed readily by column chromatography. This is
a great advantage for phthalocyanine synthesis.
With these encouraging results, we attempted to prepare a
phthalocyanine with four different isoindole units, i.e., an
ABCD-type phthalocyanine. Scheme 3 shows the convergent
route used to prepare this compound. The first half of the
phthalocyanine was derived from bisphthalonitrile 6, which was
prepared from 3-nitrophthalonitrile (3) through aromatic
nucleophilic substitution with 1,3-propanediol, tosylation
using 4-dimethylaminopyridine (DMAP) as the base, and
then monosubstitution with 2,3-dicyanohydroquinone (5). To
prepare the other half, 4,5-dichloro-3,6-dihydroxyphthalonitrile
(7) underwent Mitsunobu reaction with 1,3-propanediol,
diisopropyl azodicarboxylate (DIAD), and triphenylphos-
phine,17 followed by aromatic nucleophilic substitution with
1-butanethiol to give 8. This compound was then converted to
the ditosylate, and one of these moieties was then substituted
with the previously reported phthalonitrile 98c to yield the
bisphthalonitrile 10. The two bisphthalonitriles 6 and 10 were
then coupled by aliphatic nucleophilic substitution reaction to
give the tetrakisphthalonitrile 11 in 71% yield. By using the
same cyclization conditions as reported in Scheme 2, the
1
(Figures S1 and S2 in SI). Their H NMR spectra in CDCl3
with a trace amount of pyridine-d5 displayed well-resolved
signals, indicating that the compounds were not significantly
aggregated even in a millimolar range of concentration. For 12,
the aromatic signals were well-separated and resolved, including
a doublet at δ 9.17 for the only α proton of the phthalocyanine
ring and a virtual triplet at δ 8.03, three doublets at δ 7.77, 7.73,
and 7.53, as well as a singlet at δ 7.66 (two protons) for the six
β ring protons, which could be assigned readily as shown in
Figure 1.
The UV−vis spectrum of 2 in N,N-dimethylformamide
(DMF) (Figure S3 in SI) showed an intense and sharp Q-band
at 713 nm, which is blue-shifted by ca. 20 nm compared with
those of typical octa-α-alkoxy zinc(II) phthalocyanines.18 It is
not clear if this is due to the ring strain that may be imposed by
the linkers. With seven α-substituents and two β-substituents,
phthalocyanine 12 gave the Q-band at 716 nm (Figure 2). It
has been reported that both the substitution of alkoxy groups at
the α-positions and that of alkylthio groups at the β-positions of
phthalocyanines will shift the Q-bands to the red.19 The similar
spectral features of 2 and 12 suggest that the effect of two
additional β-butylthio groups can counteract the effect of one
α-alkoxy group on the Q-band absorption. As expected, for
both of these compounds, the Q-band strictly followed the
Lambert−Beer law, revealing their nonaggregated characteristic.
Upon excitation at 610 nm, compound 12 showed a
fluorescence emission at 725 nm with a fluorescence quantum
B
DOI: 10.1021/acs.orglett.6b01489
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
and produce low-symmetry phthalocyanines that cannot be
prepared by conventional methodologies. In addition, the sole
phthalocyanine products are isomerically pure, which can
greatly facilitate the isolation and purification.
In summary, we have developed a new strategy for the
controlled synthesis of phthalocyanines. It involves conjugation
of four preselected phthalonitrile units followed by base-
promoted intramolecular cyclization in the presence of a metal
template. The resulting phthalocyanines can be obtained in
about 7% yield. This approach is particularly useful for
synthesis of exotic phthalocyanines with a very low symmetry.
Owing to the potential intriguing properties of these
compounds, it is envisaged that this approach can greatly
enrich the chemistry of phthalocyanines.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01489.
Experimental details, synthetic scheme for 1, and
additional spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: dkpn@cuhk.edu.hk.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Sunny Y. K. Ng of our Department for preparing
some of the intermediate products and The Chinese University
of Hong Kong for financial support.
1
Figure 1. H NMR spectrum of 12 in CDCl3 with a trace amount of
pyridine-d5; the residual solvents’ signals are marked with an asterisk.
DEDICATION
■
Dedicated to Professor Tien-Yau Luh on the occasion of his
70th birthday.
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